Compositions and methods for the treatment of muscle wasting
The invention provides compositions of oligonucleotides targeted at genes involved in muscle wasting and/or muscle growth. In some embodiments, the oligonucleotides are modified. In some embodiments, the compositions contain one, or more than one, oligonucleotide. The invention also provides methods and kits using the compositions of the invention for the treatment of muscle wasting conditions and/or the promotion of muscle growth.
1. A method of treating a muscle wasting condition comprising administering to an individual suffering from a muscle wasting condition an effective amount of a composition suitable for administration to an animal comprising
a modified oligonucleotide containing 7 to 75 contiguous ribose groups linked by achiral 5′ to 3′ internucleoside phosphate linkages,
wherein the modified oligonucleotide is complementary to a region of a gene selected from the group consisting of the 5′ UTR region, translational start site, the 3′ UTR, and translational termination site, and
wherein the gene encodes FOXO1.
2. A method of promoting muscle growth in an individual comprising administering to the individual an effective amount of a composition suitable for administration to an animal comprising
a modified oligonucleotide containing 7 to 75 contiguous ribose groups linked by achiral 5′ to 3′ internucleoside phosphate linkages,
wherein the modified oligonucleotide is complementary to a region of a gene selected from the group consisting of the 5′ UTR region, translational start site, the 3′ UTR, and translational termination site, and
wherein the gene encodes FOXO1.
3. The method of claim 1 or 2 wherein the individual is a mammal.
4. The method of claim 1 or 2 wherein the individual is a human.
5. The method of claim 1 , wherein the modified oligonucleotide comprises one or more nucleotides in which the 2′ position comprises a substituent.
6. The method of claim 5 , wherein the 2′ substituent is selected from the group consisting of hydrogen, methoxy, propoxy, methoxy-ethoxy, fluorine, chlorine, bromine and iodine.
7. The method of claim 1 , wherein the modified oligonucleotide is 3′ and/or 5′ end-modified.
8. The method of claim 1 , wherein the modified oligonucleotide is 3′ and/or 5′ end-blocked.
9. The method of claim 1 , wherein the modified oligonucleotide is an antisense oligonucleotide.
10. The method of claims 1 , further comprising a plurality of modified oligonucleotides containing 7 to 75 contiguous ribose groups linked by achiral 5′ to 3′ internucleoside phosphate linkages, wherein the plurality of modified oligonucleotides are complementary to regions of a gene selected from the group consisting of the 5′ UTR region, translational start site, the 3′ UTR, and translational termination site, and wherein said gene codes for a gene product involved in a muscle wasting condition.
11. The method of claim 1 , further comprising two modified oligonucleotides containing 7 to 75 contiguous ribose groups linked by achiral 5′ to 3′ internucleoside phosphate linkages, wherein said modified oligonucleotides are complementary to regions of a gene selected from the group consisting of the 5′ UTR region, translational start site, the 3′ UTR, and translational termination site, and wherein said gene codes for a gene product involved in a muscle wasting condition.
12. The method of claim 1 , wherein said oligonucleotide comprises one or more nucleotides in which the 2′ position comprises a substituent, and wherein the modified oligonucleotide is 3′ and/or 5′ end-blocked.
13. The method of claim 2 , wherein said oligonucleotide comprises one or more nucleotides in which the 2′ position comprises a substituent, and wherein the modified oligonucleotide is 3′ and 5′ end-blocked.